Psychedelic substances, including classic serotonergic hallucinogens like psilocybin and LSD, are compounds that can produce significant changes in perception, mood, and cognition. For centuries, these substances have been used in various cultural and religious contexts. Modern science is now exploring the neurobiological mechanisms that underlie their effects on brain function and structure.
Psychedelics and Serotonin Receptors
The primary action of classic psychedelics like LSD and psilocybin is their interaction with the brain’s serotonin system. These compounds share a structural similarity with serotonin, allowing them to act as agonists at serotonin 2A (5-HT2A) receptors. The intensity of a psychedelic experience corresponds to the degree of this activation, which is the principal source of their hallucinogenic effects.
This binding process initiates a cascade of downstream signaling events within neurons. The 5-HT2A receptor is a G-protein-coupled receptor, and its activation by a psychedelic molecule triggers specific intracellular pathways that differ from those triggered by serotonin itself. This unique signaling is believed to be the foundation for the subsequent large-scale changes in brain activity and the resulting alterations in consciousness.
Rewiring Brain Networks
The activation of 5-HT2A receptors by psychedelics leads to temporary alterations in large-scale brain communication. Neuroimaging studies using techniques like fMRI have revealed that these substances disrupt established patterns of brain connectivity. One of the most consistent findings is the reduction in the activity and coherence of the Default Mode Network (DMN), a group of interconnected brain regions active during inward-focused thought.
The disintegration of the DMN is a hallmark of the psychedelic state. This network helps maintain our sense of a stable self, or “ego,” and its disorganization is strongly correlated with the experience of “ego dissolution.” As the DMN’s influence wanes, communication becomes less hierarchical, and brain regions that do not normally interact begin to show increased connectivity.
This state of increased global integration is often described as an increase in “brain entropy.” The brain’s activity becomes more random and less predictable, a state that some researchers compare to the dynamic consciousness of early childhood. This increase in neural entropy is thought to underlie the novel patterns of thought and perception that characterize the psychedelic experience.
Stimulating Neural Plasticity
Beyond the immediate changes in brain network activity, psychedelics also appear to promote neural plasticity, which is the brain’s ability to reorganize its structure and function. Research indicates that these compounds can stimulate the growth of new connections between neurons. This process includes the formation of new synapses and the growth of dendritic spines.
This effect is also linked to the activation of 5-HT2A receptors, which can trigger intracellular signaling cascades that support neuronal growth. A molecule in this process is Brain-Derived Neurotrophic Factor (BDNF), a protein involved in neuron survival and growth. Studies have shown that psychedelics can increase the expression of genes related to plasticity and boost levels of BDNF.
These plastic changes can outlast the acute effects of the drug. For instance, animal studies have demonstrated that a single dose of a psychedelic can lead to a sustained increase in dendritic spine density in cortical neurons. This capacity to promote structural and functional neural plasticity is a focus of current research, as it suggests a mechanism by which these substances might facilitate lasting changes in brain function.
How Brain Activity Shapes Psychedelic Experiences
The heightened and disorganized brain entropy contributes to the fluid and unpredictable nature of psychedelic consciousness. This increased connectivity between different brain modules can explain phenomena like synesthesia, where senses merge, or the vivid, complex visual hallucinations that are often reported. For instance, increased communication between the visual cortex and brain regions involved in emotion and memory can lead to the perception of emotionally charged and meaningful imagery.
The initial binding to 5-HT2A receptors sets off the entire cascade, from network disintegration to the novel sensory experiences. The stimulation of neural plasticity may also relate to the enduring shifts in perspective and insight that users sometimes report long after the substance has left their system. By linking specific neural events to distinct aspects of the psychedelic experience, researchers are beginning to build a comprehensive model of how these substances produce their unique effects on the human mind.